The proposed research is directed towards an improved understanding of conformational states of, and conformational transitions in, proteins and homopoly-alpha-amino acids through a study of the effect of hydrostatic pressure on solutions of these polypeptides. We describe an inter-institutional collaboration which seeks to take advantage of the combination of certain unique experimental facilities developed at Penn. State University, with a newly evolved thermodynamic treatment of conformational transitions in an analysis of the data expected as a result of the proposed program. The aforementioned instrumentation permits the measurement, essentially for the first time, of the optical rotatory dispersion and circular dichroism of the macromolecules of interest in dilute solution up to several thousand atmospheres pressure. We will thereby determine directly the conformational states as a function of extrinsic variables such as pressure, temperature, solvent, etc., and hence delineate the respective phase boundary surfaces. It is intended to study order-disorder transitions in selected polyglutamic acid esters in organic solvent systems, in the queous soluble but nonionized poly-omega-alklyhydroxyglutamines, and in lysozyme. The relevant optical properties of these solvated macromolecules will be investigated per se as part of the program. The analysis referred to above has permitted the resolution of experimental ambient pressure data for homopolypeptides into separate inter-peptide and peptide-solvent(s) interactions. Hence we have been able to assess in a relatively definitive manner the precise contributions of sidegroup structure to the intrinsic conformational stability of several polypeptides. The analysis has recently been extended to include the effect of pressure and it is postulated that application of the concept to experimental results in the research described will significantly broaden the scope and utility of the work. The longer term objective of this study is to provide an a priori accounting of the conformational stability of a protein or enzyme in a given environment as a function of its structure, to thereby gain a molecular level understanding of its in vivo function, and where appropriate to identify structural errors in such polymers which may be responsible for deviant physiological behavior.